Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the effect of beta 1-blockade (metoprolol) on the plasma glucose thresholds initiating counterregulatory hormone responses and symptoms of hypoglycemia, we used a modified glucose clamp technique to produce a standardized gradual glucose decline from 5.0 to 2.0 mmol/l in nine patients with insulin-dependent diabetes mellitus (IDDM) (HbAlc range 6.7-10.3%, duration of diabetes 5-18 years, autonomous neuropathy present in three of the patients). The responses were studied once with metoprolol and once with placebo, in random order. With the beta 1-selective blockade, epinephrine release was triggered at a significantly higher (p less than 0.02) plasma glucose level (3.5 mmol/l) than it was with placebo (3.0 mmol/l). Metoprolol did not change thresholds for growth hormone (3.7/3.5 mmol/l), cortisol (2.9/2.9 mmol/l), glucagon (2.8/2.8 mmol/l) or for pancreatic polypeptide (2.8/2.7 mmol/l). The peak responses of epinephrine and growth hormone were significantly higher (p less than 0.01) with the beta 1-blockade. Metoprolol did not change the thresholds for neuroglycopenic and autonomic symptoms. Six out of the seven patients who answered yes to having hypoglycemia did so at a higher blood glucose with metoprolol than without. In our study, the beta 1-selective blockade altered the responses of counterregulatory hormones, but it did not change the thresholds for hypoglycemic symptoms.
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PMID:The effect of selective beta 1-blockade on glucose thresholds for release of counterregulatory hormones and symptoms in insulin-dependent diabetes mellitus. 134 50

Herein we describe what is, to our knowledge, the first reported case of a composite tumor of the main bile duct with epiploon metastases. Glucagon, pancreatic polypeptide, and somatostatin-immunoreactive cells were demonstrated in these metastases, but not serotonin, gastrin, or insulin-immunoreactive cells. The clinical significance of the neuroendocrine cells in the present case is discussed.
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PMID:Composite tumor of the main bile duct producing several regulatory peptides. 135 Jul 7

The presence of insulin, glucagon, pancreatic polypeptide, and somatostatin containing cells and their ontogenic changes were investigated immunocytochemically in the early fetal pancreas of the guinea pig (Days 25-40). In the earliest tissues examined (Day 25 and Day 30) brightly staining glucagon cells were the most predominant endocrine cell population, followed by slightly fewer and weaker staining pancreatic polypeptide cells. Insulin and somatostatin immunoreactive cells were less numerous. At Day 25 all endocrine cells were located within the pancreatic tubules where some glucagon cells also coexpressed insulin. Similar dual immunoreactivity was present at Day 30. At Day 25 some of the pancreatic polypeptide cells also showed coexpression of somatostatin which persisted until Days 35-40. At these later stages insulin and somatostatin cells were increasingly frequent. Glucagon and pancreatic polypeptide cells were also conspicuous. The four endocrine cell types were found either in the pancreatic tubules or in the developing islets where they began to acquire an adult-like topographic distribution. These studies in the fetal guinea pig show that the four islet hormonal cells cytodifferentiate from an early stage. A small proportion of endocrine cells coexpress either insulin and glucagon or pancreatic polypeptide and somatostatin.
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PMID:An immunocytochemical study of endocrine cell development in the early fetal guinea pig pancreas. 135 Oct 15

Fifty exocrine pancreatic adenocarcinomas and 57 benign tumors induced in Syrian hamsters by N-nitrosobis(2-oxopropyl)amine (BOP) were examined for the presence of argyrophil cells antiinsulin, -glucagon, -somatostatin, -pancreatic polypeptide (PP), -gastrin/CCK, -vasoactive intestinal polypeptide (VIP), and - neuron-specific enolase (NSE) reactive cells. Argyrophil - and antihormone-reactive cells were found in the normal pancreatic ducts and in the acini, as well as in hyperplastic and atypical ducts/ductules, tubular complexes, benign lesions, and in 80% of ductal adenocarcinomas. Insulin and antiNSE-reactive cells were the most common, followed in decreasing frequency by glucagon, somatostatin, and PP cells. Antigastrin-/CCK-and -VIP-reactive cells were found in two cases. Argyrophil cells were present in about 60% of the tumors with Grimelius staining and in 55% of those with Churukian-Schenk staining. Insulin cells were seen in ductal cancer that had grown into a lymph node and in the lymph node metastases of another cancer. A novel finding was the presence of argyrophil and insulin cells within the lumen of some malignant glandular structures. Coexistence of several peptide cells was found in 52% of the cancers. The presence of argyrophil and hormone-producing cells in induced pancreatic ductal/ductular lesions further strengthens the existence of a close developmental relationship between exocrine and endocrine cells of the pancreas.
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PMID:Immunohistochemical characterization of endocrine cells in experimental exocrine pancreatic cancer in the Syrian golden hamster. 135 11

The expression of the genes encoding the hormones glucagon, insulin, somatostatin, and pancreatic polypeptide in the endocrine islets of the pancreas is regulated in a cell-specific manner, defining four distinct cellular phenotypes (A-, B-, D-, and F-cells, respectively). Binding of nuclear proteins to cognate DNA sequences within cis-acting regulatory elements mediates the transcriptional events that result in the cell-specific activation or repression of gene expression. In a parallel study, we describe the functional properties of the SMS-UE, a pancreatic islet D-cell specific enhancer element that regulates the expression of the somatostatin gene and contains two interdependent domains, A and B. In the studies described herein, we have characterized the nuclear proteins that recognize the SMS-UE. Domain A of the SMS-UE is a DNA enhancer sequence that is identical to that bound by the ubiquitously distributed CCAAT box-binding protein alpha-CBF, a transcription factor that regulates the expression of the human chorionic gonadotrophin alpha-subunit gene. The B-domain, on the other hand, binds an islet cell-specific protein with characteristics similar to those of Isl-1, a transcriptional activator protein that binds to the E2 enhancer of the rat insulin-1 gene. In addition, the SMS-UE binds transcription factor CREB but not CREM, the close homolog of CREB, on a site adjacent to, or overlapping, the 3' end of domain B. We show that the carboxyl-terminal bZIP domain of CREB binds to the cAMP response element of the somatostatin gene but is not sufficient for binding to the SMS-UE, and we present evidence suggesting that CREB.SMS-UE binding requires stabilization by a region of the protein located within the transactivation domain.
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PMID:Somatostatin gene upstream enhancer element activated by a protein complex consisting of CREB, Isl-1-like, and alpha-CBF-like transcription factors. 135 92

The endocrine pancreas of the Australian fat-tailed dunnart (Sminthopsis crassicaudata) was investigated by means of immunocytochemistry using the avidin-biotin-peroxidase technique. This was a light microscopic study using this established technique and has not been previously investigated. Serial paraffin sections were stained individually with primary antibodies for anti-porcine glucagon, anti-beef pork insulin, anti-human somatostatin, and anti-avian pancreatic polypeptide (APP), anti-bovine pancreatic polypeptide (BPP), anti-serotonin, anti-porcine motilin, showing the same islet. Cells immunoreactive to porcine glucagon, porcine insulin, human somatostatin, APP, BPP were found in endocrine islets, but BPP and APP also appear to be scattered amidst the exocrine portion. Immunoreactive cells were not observed with serotonin and anti-porcine motilin. All controls were negative. These results in the dunnart pancreas has shown four types of pancreatic endocrine cells. It has also shown that the structure of PP may more closely resemble BPP than APP. This study can be related to studies in echidnas (Tachyglossus aculeatus) and Australian possum (Trichosurus vulpecula). This is a part of an immunocytochemical study investigating the endocrine pancreas in Australian mammals.
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PMID:A light-microscopic immunocytochemical study of the endocrine pancreas in the Australian fat-tailed dunnart (Sminthopsis crassicaudata). 135 14

The cellular composition and relative frequency of the occurrence of pancreatic endocrine cells were studied immunohistochemically in a primitive eutherian and arboreal folivore, the three-toed sloth, since previous histochemical and ultrastructural studies on the endocrine pancreas of the sloth have detected only a single islet cell type, the A cell. In the sloth pancreas, four types of endocrine cells immunoreactive for glucagon, insulin, somatostatin and serotonin (5-hydroxytryptamine) were found as reported in the pancreas of human and common experimental mammals, but pancreatic polypeptide-immunoreactive cells were not detected by either avian- or bovine-pancreatic polypeptide antiserum. The endocrine cells were distributed mainly in the islets and partly also in the exocrine tissue including the pancreatic ducts. Larger or smaller clusters consisting of glucagon- and insulin-immunoreactive cells were also found frequently in the interlobular connective tissue. In the islets, glucagon- and insulin-immunoreactive cells were the most prominent cell type, while somatostatin- and serotonin-immunoreactive cells were sparse. The most striking feature in the sloth pancreas is the high frequency of glucagon-immunoreactive cells, because these cells are by far less in number than insulin-immunoreactive cells in the islets of human and common experimental mammals. This appears to be an intriguing characteristic of the sloth pancreas in a possible relation to the animal's unique metabolic system and the phylogenetical position.
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PMID:An immunohistochemical study on the pancreatic endocrine cells of the three-toed sloth, Bradypus variegatus. 135 79

Most, if not all, endocrine cells seem capable of synthesizing and storing more than one hormone. Such cellular colocalization of hormones can be due either to the presence of two or more specific granules within the cells or to colocalization of the hormones within a single granule. The present study was performed to clarify the subcellular localization of insulin, glucagon, somatostatin, and pancreatic polypeptide within the endocrine cells of the human and porcine pancreas during fetal development, with special reference to possible colocalization of the hormones. The tissue specimens were processed for ultrastructural cytochemistry using Lowicryl as embedding medium. An immunogold labeling technique was used with two parallel, but not interacting, antibody chains. Sections from each specimen were double labeled in different combinations giving a complete covering of the four major islet hormones. During fetal life (50-90 days prenatally in porcine pancreas, 14 weeks gestation in the human pancreas) several hormones were demonstrated, not only in the same endocrine cells, but also in the same secretory granules (polyhormonal granules). Costorage of insulin, glucagon, somatostatin, and pancreatic polypeptide was demonstrated in granules in pancreatic endocrine fetal cells. At an early fetal stage, the endocrine cells contained either dense, round granules or pale, heteromorphous granules. With increasing age and maturation of the endocrine cells, structural differentiation of the secretory granules was found to be associated with a gradual disappearance of the polyhormonal granules. The first genuine monohormonal cell to appear in the porcine fetus was the pancreatic polypeptide cell (at 70 days gestation); it was followed by the somatostatin-producing endocrine cell. Mature insulin- and glucagon-producing cells were only demonstrated after birth. Thus, in the adult pancreatic endocrine cells, each specific endocrine cell type produced only one of the four classical hormones. The present investigation demonstrated that the endocrine cells of the fetal, but not the adult, pancreas are able to synthesize all the major islet hormones, and that these peptides are costored in the same granule. The data obtained support the concept of a common precursor stem cell for pancreatic hormone-producing cells.
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PMID:Ultrastructural studies of the ontogeny of fetal human and porcine endocrine pancreas, with special reference to colocalization of the four major islet hormones. 135 60

The comparative morphology of the endocrine pancreas was studied in 11 species of lacertids. Four major cell types were identified immunocytochemically in the endocrine pancreas: glucagon-immunoreactive A-cells, insulin-immunoreactive B-cells, somatostatin-(SRIF)-immunoreactive D-cells, and pancreatic polypeptide(PP)-immunoreactive F-cells. Different distributions of the four cell types were seen in the endocrine tissue within the exocrine parenchyma. F-cells were rare or absent in the splenic lobe and abundant in the duodenal lobe, in which they were usually widespread in the exocrine parenchyma and rarer in the islets. The other three cell types were always present in the islets. The central core consisted of B- and A-cells, with B-cells predominating. The peripheral mantle was formed by A-cells and less abundant D-cells. Rare D-cells were also found in the central core. D- and F-cells showed projections often closely associated with capillaries. The observed arrangements in islets and isolated cells may represent an endocrine network that, in addition to systemic actions, may regulate exocrine function in a paracrine fashion.
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PMID:An immunocytochemical study of the endocrine pancreas in three genera of lacertids. 135 81

Among 33 patients with endocrine pancreatic tumors due to multiple endocrine neoplasia type 1 (MEN-1), 19 (58%) patients had hypergastrinemia, 7 (21%) patients had hyperinsulinism, and 7 (21%) patients had clinically non-functioning lesions. At least one gross tumor was found in all patients undergoing pancreatic surgery, including those with negative localization studies prior to operation. The patients also had additional macroscopic tumors as well as numerous microadenomas, and the lesions frequently were positive for immunostaining with multiple hormones, mainly pancreatic polypeptide, insulin, glucagon, and somatostatin. Duodenal endocrine lesions were found in 4 of 5 investigated patients and stained with gastrin and somatostatin antibodies. Distal, mainly subtotal pancreatic resection, was performed in 18 patients, eventually combined with caput tumor enucleation or duodenotomy, while a few patients underwent only tumor enucleation or a Whipple procedure. The long-term outcome of operation was most favorable in patients with hyperinsulinism; only 1 patient had clinical recurrence. Patients with hypergastrinemia experienced only transitory lowering of serum gastrin values after pancreatic surgery and 47% of them had or developed metastases. Such tumor spread was seen in 57% of the patients with non-functioning lesions. Nine patients died from progressive tumor disease during follow-up. Consistent with previous studies, we found that surgery is indicated in MEN-1 patients with hyperinsulinism even if a lesion is not visualized by radiology. In addition, these indications should be extended to also include patients with only biochemical markers of disease, including elevations of gastrin, as these indicate the presence of gross tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pancreatic tumors in multiple endocrine neoplasia type 1: clinical presentation and surgical treatment. 135 27


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